The mitochondrial tRNA(Leu(UUR)) mutation in mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS): genetic, biochemical, and morphological correlations in skeletal muscle.

Abstract

Mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) has recently been associated with an A----G transition at position 3243 within the mitochondrial tRNA(Leu(UUR)) gene. Besides altering the tRNA(Leu(UUR)) sequence, this point mutation lies within a DNA segment responsible for transcription termination of the rRNA genes. We have studied the distribution and expression of mutant mtDNAs in muscle biopsies from MELAS patients. Histochemical, immunohistochemical, and single-fiber PCR analysis showed that ragged-red fibers (RRF) are associated both with high levels of mutant mitochondrial genomes (greater than 85% mutant mtDNA) and with a partial cytochrome c oxidase deficiency. By quantitative in situ hybridization, the steady-state ratios of mRNAs:rRNAs were found to be similar to controls in six of eight patients studied. In two other patients the relative levels of heavy-strand mRNAs were slightly increased, but a patient with myoclonic epilepsy and RRF also exhibited a similar increase. These results directly correlate the A----G transition at mtDNA position 3243 with muscle mitochondrial proliferation, partial respiratory-chain impairment, decreased mitochondrially synthesized protein content, and no specific alterations in mitochondrial ratios of mRNAs:rRNAs.

• Authors: C T Moraes, E Ricci, E Bonilla, S DiMauro, E A Schon
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 50 Issue 5 Pg. 934-49 (May 1992) ISSN: 0002-9297 [Print] United States
• PMID: 1315123 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Mitochondrial
• RNA, Transfer, Leu
• Electron Transport Complex IV

Topics

• Acidosis, Lactic (genetics, metabolism, pathology)
• Adult
• Cerebrovascular Disorders (genetics, metabolism, pathology)
• DNA, Mitochondrial (genetics)
• Electron Transport Complex IV (metabolism)
• Female
• Gene Expression (genetics)
• Humans
• Immunohistochemistry
• Male
• Mitochondria, Muscle (metabolism, pathology)
• Muscles (metabolism, ultrastructure)
• Mutation (genetics)
• Neuromuscular Diseases (genetics, metabolism, pathology)
• Nucleic Acid Hybridization
• Polymerase Chain Reaction
• RNA, Transfer, Leu (genetics)